Here, I propose to use the Molecular Epidemiology of Colorectal Cancer (MECC) study, a large population-based case-control study of colorectal cancer in northern Israel, to investigate methylation status in colorectal cancer. The overall hypothesis of this proposal is that methylation status represents a distinct group of CRCs that may independently predict overall survival from CRC. Specifically, the goals are to: 1. Measure the prevalence of hypermethyled genes in sporadic CRC by comparing the methylation panel on available tumor and normal samples (approximately 1450 paired samples) from MECC cases; 2. Determine if patterns of hypermethylation represent distinct subgroups of CRC; 3. Evaluate hypermethylation as an independent prognostic factor in CRC: a. Using Israeli national registries and vital statistics compare survival in subjects; b. Measure survival in the presence of other classically reported prognostic factors. This research addresses the question of whether methylation status defines a subset of tumors with distinct genetic, epigenetic and clinicopathologic characteristics in the general population.